PB2436: EFFICACY AND SAFETY PROFILE OF EVEROLIMUS AS A MAINTENANCE THERAPY FOR PRIMARY REFRACTORY/RELAPSING HODGKIN LYMPHOMA FOLLOWING AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION
Authors: Shayan Zamani, Hamed Azhdari, Mahshid Mehdizadeh
Journal: HemaSphere (2023)

Topic: 22. Stem cell transplantation - Clinical Background: Patients with relapsing or primary refractory Hodgkin lymphoma (HL), still have unsatisfactory outcomes after high dose chemotherapy followed by autologous hematopoietic stem cell transplantation (HSCT). Brentuximab vedotin is approved for maintenance therapy for up to one year in these patients, however, this agent is not yet easily available and affordable in many settings especially in developing countries. There is a need for finding alternatives to address patients’ medical demand. Aims: we evaluated efficacy and safety profile of everolimus as a possible alternative option for maintenance therapy after autologous HSCT among patients with relapsing/refractory HL. Methods: This was a prospective study from June 2016 to June 2021, which targeted patients with primary refractory/ relapsing HL who underwent autologous HSCT. The inclusion criteria were: age ≥ 18; patients with HL who were in partial remission 2 (PR2) or beyond, or, patients who never reached complete remission (CR1); patients who had received at least 3 different chemotherapy regimens before HSCT; glomerular filtration rate > 30 ml/min/1.73 m2; ejection fraction ≥ 50%; liver enzymes less than 3 times upper normal; disease-free status for at least 3 months post autologous HSCT; and lack of access to brentuximab vedotin. The exclusion criteria were: Patients who did not consent to this trial, history of allergy to mammalian target of rapamycin (mTOR) inhibitors, severe adverse effects not acceptable by the patients. Transplantation protocol was in the following manner. Conditioning regimen was either LEAM (Lomustine + Etoposide + Cytarabine + Melphalan), or, BeAEM (Bendamustine + Etoposide + Cytarabine + Melphalan). Disease status was reevaluated on day +90 post-HSCT, using computed tomography or positron emission tomography. Patients with no disease progression were chosen for treatment with everoilmus at dose of 10 mg daily. The needed time of maintenance therapy is at least 2 years. Patients were followed for disease status and drug side effects monthly for the first 3 months and then each 3 months. Results: we collected and assessed the clinical data of 20 patients who underwent autologous HSCT. The median age was 29.05 years (18-47). 13 patients had advanced HL, 7 had early-stage disease before transplant. Out of the 7 early-staged patients 2 had mediastinal mass and 5 had B symptoms, both known as unfavorable risk factors for unsuccessful transplantation. Out of the 20 patients, 17 and 3 patients had partial response and complete response to salvage chemotherapy prior to the HSCT, respectively. Five patients had received brentuximab vedotin previously as a salvage therapy but did not meet the favorable response. Three months post-transplant, 13 patients reached CR in the imaging evaluation. On the other hand, 7 patients still had evidence of residue. Patients were followed for a median of 29.9 months (9-51). The median duration of treatment was 22.95 months (range: 6 – 48 months). Patients had certain adverse effects with 10 mg/d dose of everolimus, the dose was reduced to 5 mg/d for these patients, these Adverse effects are shown in Table 1. Mucocutaneous presentations were the most common adverse effect. One patient relapsed. Others had no progression and are still receiving everolimus (95%). We did not have any mortality due to disease recurrence. Summary/Conclusion: This was the first study to evaluate everolimus as a maintenance therapy for relapsed/refractory HL. Findings of this study support the promising effects of everolimus in patients with relapsing or primary refractory Hodgkin lymphoma after autologous HSCT.Keywords: Maintenance, Hodgkin’s lymphoma, Autologous hematopoietic stem cell transplantation, relapsed/refractory